The causes and contributing factors for autism are poorly understood. Evidence suggests that incidence is increasing, but diagnostic changes & improvements may be playing a role. Both genetic and environmental factors appear to play a role. Autopsy studies demonstrate structural changes in the brain and clinical investigations reveal neurophysiologic differences in information processing in autistic vs. normal children. Members of our team recently demonstrated altered levels of certain neuropeptides at birth in children who later developed autism. The proposed case-control study will be the first large-scale epidemiologic investigation of underlying causes for autism and triggers of regression. This study will capitalize on the strengths of the case-control design, which is well suited to examine a broad array of factors for rare conditions that are thought to be multifactorial. Comparisons will be made with both general population controls and mentally retarded children. From California's Department of Developmental Services (DDS) databases and Regional Centers that coordinate services for developmentally disabled persons, we will identify children aged 2 to 5 years, recently diagnosed with autism from two geographic areas in the state. Eligibility will be determined through evaluation by trained professionals using the Autism Diagnostic Interview-Revised and the Autistic Diagnostic Observation Schedule-Generic. A set of general population controls will be matched on gender, age, and community of residence. Another set will be matched to the autistic children with mental retardation, and will consist of children in the DDS database/Regional Center system with mental retardation but not autism. Cognitive and adaptive function will be assessed in all children. Both parents will be interviewed, separately, regarding peri- conceptional, prenatal, and early childhood exposures and experiences. Interviewers will collect family histories of speech development, social skills, psychological disorders, and behavioral patterns. Blood, urine, and buccal swab specimens will be collected from the index child (case or control), parents, and siblings, and newborn blood spots from the index child will be obtained from the specimen bank maintained by the State of California. Prenatal clinic, delivery, and pediatric medical records for the index child will be obtained. Specimens will be analyzed by the Analytical Biomarkers Core for mRNA of candidate genes and later for specific genetic polymorphisms. The proposed study will be the first major epidemiologic case-control study to examine autism in relation to a broad array of environmental exposures and endogenous susceptibility factors.